A recently published study on halogen bonding in casein kinase 2 (CK2)-inhibitor complexes claimed that the halogen-bond-corrected PM6 semiempirical method (PM6-DH2X) describes the halogen bonding properties correctly, whereas the AMBER empirical potential fails. The current study employs our positive extra-point (PEP) approach for halogen bonding, in which the a-hole on the halogen atom is represented by an extra point of charge. The performance of the two methods in describing halogen bonding in halobenzene center dot center dot center dot Lewis base and CK2-inhibitor complexes was reassessed. Compared to basis set superposition error- (BSSE-) corrected MP2/aug-cc-pVDZ (with PP functions on the Br and I atoms) data, the AMBER force field described the halogen bonding in halobenzene center dot center dot center dot Lewis base complexes slightly better than the PM6-DH2X method. Fifteen polyhalogenated benzimidazole inhibitors (taken from a study of Dobes et al.) complexed to CK2 protein were studied. The binding energies were calculated using the molecular mechanical-generalized Born surface area (MM-GBSA) approach. Compared to the corresponding experimental data, the AMBER force field yielded much better PM6-DH2X method. Finally, the performance of both methods in describing C-X center dot center dot center dot pi-system and C-X center dot center dot center dot H-O/C interactions was examined. A comparison with MP2 data revealed that the PM6-DH2X method failed to describe them, whereas the AMBER force field performed well.